Determination of biomarker candidates for the placenta accreta spectrum by plasma proteomic analysis.

Placenta accreta spectrum (PAS) presents a significant obstetric challenge, associated with considerable maternal and fetal-neonatal morbidity and mortality. Nevertheless, it is imperative to acknowledge that a noteworthy subset of PAS cases remains undetected until the time of delivery, thereby contributing to an augmented incidence of morbidity among the affected individuals. The delayed identification of PAS not only hinders timely intervention but also exacerbates the associated health risks for both the maternal and fetal outcomes. This underscores the urgency to innovate strategies for early PAS diagnosis. In this study, we aimed to explore plasma proteins as potential diagnostic biomarkers for PAS. Integrated transcriptome and proteomic analyses were conducted to establish a novel diagnostic approach. A cohort of 15 pregnant women diagnosed with PAS and delivering at Inonu University Faculty of Medicine between 01/04/2021 and 01/01/2023, along with a matched control group of 15 pregnant women without PAS complications, were enrolled. Plasma protein identification utilized enzymatic digestion and liquid chromatography-tandem mass spectrometry techniques. Proteomic analysis identified 228 plasma proteins, of which 85 showed significant differences (P < 0.001) between PAS and control cases. We refined this to a set of 20 proteins for model construction, resulting in a highly accurate classification model (96.9% accuracy). Notable associations were observed for proteins encoded by P01859 (Immunoglobulin heavy constant gamma 2), P02538 (Keratin type II cytoskeletal 6A), P29622 [Kallistatin (also known as Serpin A4)], P17900 (Ganglioside GM2 activator Calmodulin-like protein 5), and P01619 (Immunoglobulin kappa variable 3-20), with fold changes indicating their relevance in distinguishing PAS from control groups. In conclusion, our study has identified novel plasma proteins that could serve as potential biomarkers for early diagnosis of PAS in pregnant women. Further research and validation in larger PAS cohorts are necessary to determine the clinical utility and reliability of these proteomic biomarkers for diagnosing PAS.

Performance improvement of GaN-based microdisk lasers by using a PEALD-SiO2 passivation layer.

Dry-etching is often utilized to shape GaN-based materials. However, it inevitably causes plenty of sidewall defects as non-radiative recombination centers and charge traps that deteriorate GaN-based device performance. In this study, the effects of dielectric films deposited by plasma-enhanced atomic layer deposition (PEALD) and plasma-enhanced chemical vapor deposition (PECVD) on GaN-based microdisk laser performance were both investigated. The results demonstrated that the PEALD-SiO2 passivation layer largely reduced the trap-state density and increased the non-radiative recombination lifetime, thus leading to the significantly decreased threshold current, notably enhanced luminescence efficiency and smaller size dependence of GaN-based microdisk lasers as compared with the PECVD-Si3N4 passivation layer.

Endometrial Cancer Individualized Scoring System (ECISS): A machine learning-based prediction model of endometrial cancer prognosis.

OBJECTIVE: To establish a prognostic model for endometrial cancer (EC) that individualizes a risk and management plan per patient and disease characteristics. METHODS: A multicenter retrospective study conducted in nine European gynecologic cancer centers. Women with confirmed EC between January 2008 to December 2015 were included. Demographics, disease characteristics, management, and follow-up information were collected. Cancer-specific survival (CSS) and disease-free survival (DFS) at 3 and 5 years comprise the primary outcomes of the study. Machine learning algorithms were applied to patient and disease characteristics. Model I: pretreatment model. Calculated probability was added to management variables (model II: treatment model), and the second calculated probability was added to perioperative and postoperative variables (model III). RESULTS: Of 1150 women, 1144 were eligible for 3-year survival analysis and 860 for 5-year survival analysis. Model I, II, and III accuracies of prediction of 5-year CSS were 84.88%/85.47% (in train and test sets), 85.47%/84.88%, and 87.35%/86.05%, respectively. Model I predicted 3-year CSS at an accuracy of 91.34%/87.02%. Accuracies of models I, II, and III in predicting 5-year DFS were 74.63%/76.72%, 77.03%/76.72%, and 80.61%/77.78%, respectively. CONCLUSION: The Endometrial Cancer Individualized Scoring System (ECISS) is a novel machine learning tool assessing patient-specific survival probability with high accuracy.

High expression of CD8 in the tumor microenvironment is associated with PD-1 expression and patient survival in high-grade serous ovarian cancer.

Objective: The current study assesses programmed death-1 (PD-1) receptor expression and CD3, CD4, and CD8 tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSOC) and associates our results with neoadjuvant chemotherapy history and disease prognosis. Materials and Methods: We included cases diagnosed with primary HGSOC with biopsy or surgical resection materials in this study. The immunoreactivity of CD3, CD4, CD8, and PD1 was assessed immunohistochemically in tumor tissue. We analyzed TILs in two predetermined groups of high and low TIL. The relationships between clinical characteristics, PD-1, and TIL were assessed. by the χ(2) test or Fisher's Exact test. We used Kaplan-Meier survival analysis and Cox proportional hazards regression model to the connection between survival and the amounts of TIL, and PD1. Results: Univariate analysis demonstrated that optimal debulking (p<0.001), early International Federation of Gynecology and Obstetrics stage (p=0.046), and higher scores of stromal CD8+ TIL expression (p=0.028) in tumor cells were all substantially correlated with longer disease-free survival (DFS), whereas the remaining variables analyzed, including PD-1 positivity, stromal CD3+, and CD4+ TILs, and intraepithelial CD3+, CD4+, and CD8+ TILs, were not correlated with DFS. Also, univariate analysis revealed that optimal debulking (p=0.010), and higher scores of stromal CD8+ TIL expression (p=0.021) in tumor cells were all substantially correlated with longer overall survival (OS). Conclusion: Higher scores of stromal CD8+ TILs are substantially correlated with DFS and OS in univariate analyses, whereas scores of stromal CD3+ and CD4+ TILs, and intraepithelial CD3+, CD4+, and CD8+ TILs are not correlated with DFS and OS in both univariate and multivariate analyses. Also, we found a significant association between PD-1 positivity and the scores of stromal CD3+ TILs and intraepithelial CD8+ TILs. However, no remarkable relationship was revealed between PD-1 positivity and the survival of HGSOC cases.

Metabolomic analysis of endometrial cancer by high-resolution magic angle spinning NMR spectroscopy.

PURPOSE: To analyze endometrial metabolite profiles between patients with endometrial cancer and controls. METHODS: Seventeen (17) women with endometrium cancer and 18 controls were enrolled in this study. 1H HR-MAS (High Resolution-Magic Angle Spinning) NMR (Nuclear Magnetic Resonance) spectroscopy data obtained from endometrial tissue samples of patients with endometrial cancer and control group were analyzed with bioinformatics methods. RESULTS: Principal component analysis (PCA) and the partial least squares discriminant analysis (PLS-DA) score plots obtained with the multivariate statistical analysis of pre-processed spectral data shows a separation between the samples from patients with endometrial cancer and controls. Analysis results suggest that the levels of lactate, glucose, o-phosphoethanolamine, choline, glycerophosphocholine, phosphocholine, leucine, isoleucine, valine, glutamate, glutamine, n-acetyltyrosine, methionine, taurine, alanine, aspartate and phenylalanine are increased in patients with endometrial cancer compared to the controls. CONCLUSION: The metabolomics signature of patients with endometrial cancer is different from that of benign endometrial tissue.

Analysis of prognostic factors in Grade 3 endometrioid type endometrial carcinoma.

OBJECTIVE: To investigate the prognostic factors of patients with Grade 3 endometrioid endometrial cancer (G3EEC). METHODS: This four-center, retrospective study included a total of 129 women with G3EEC. Demographic, clinicopathologic, and survival data were collected. Kaplan-Meier method was used for survival analysis. Predictors of outcome were analyzed using Cox proportional hazards models. RESULTS: Median age at the time of diagnosis was 63 (range 39-87) years and median follow up was 37 (range 6-126) months. For the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) were 54.3% and 63.6%, respectively. The 5-year DFS rates for lymphovascular space invasion (LVSI) -positive and -negative patients were 41.6% and 88.3%, respectively (P < 0.001). The 5-year OS rates for LVSI-positive and -negative patients were 54.7% and 88.3%, respectively (P = 0.001). Positive LVSI status was identified as the independent prognostic factor for decreased DFS and OS (hazard ratio [HR] 5.5, 95% confidence interval [CI] 1.65-18.86; P = 0.006 versus HR 4.4, 95% CI 1.33-14.58; P = 0.013, respectively). CONCLUSION: LVSI seems to be an independent prognostic factor for decreased DFS and OS in G3EEC patients.

Comparison of the Retention of Conventional and Polyvinyl Siloxane Matrix Materials with Different Patrices for Implant-Retained Overdentures: An In Vitro Study.

PURPOSE: To compare the retention forces of implant overdenture patrices (ball, bar, and TiSi.snap) to conventional (O-ring, metal housing, and clip) and polyvinyl siloxane (PVS)-based silicone (retention.sil 200, 400, and 600; Mucopren Soft; and GC Reline Soft) matrix materials. MATERIALS AND METHODS: Two implant analogs, in which the patrices were to be placed, were embedded parallel to each other in polyethylene blocks, and the matrices were placed in heatpolymerized acrylic blocks that were fabricated as overdentures. Ten samples were prepared for each attachment type, and 180 samples were obtained from 18 groups. All samples were placed in a chewing simulator for occlusal force application and for insertion and removal of the pieces. Retention measurements were performed with a universal testing device at the initial (10 cycles), simulated first-year (1,825 cycles), and simulated second-year (3,650 cycles) periods, assuming that the patients would insert and remove their overdenture five times daily. RESULTS: Loss of retention occurred in all the attachment systems at the end of 3,650 cycles (P < .05). The PVS matrix materials showed less retention than the O-ring and metal matrices when a ball patrix was used, while they had higher retention than bar clips when the Hader bar patrix was used (P < .05). Among the PVS matrix materials, retention.sil 200 produced the lowest retention values, whereas retention.sil 600 generated the highest. CONCLUSION: PVS matrix materials show higher retention than that achieved by yellow plastic bar matrices. However, these materials exhibit lower retention than with plastic and metal matrices of ball abutments.

Prediction of clinical outcomes in women with placenta accreta spectrum using machine learning models: an international multicenter study.

INTRODUCTION: Placenta accreta spectrum is a major obstetric disorder that is associated with significant morbidity and mortality. The objective of this study is to establish a prediction model of clinical outcomes in these women. MATERIALS AND METHODS: PAS-ID is an international multicenter study that comprises 11 centers from 9 countries. Women who were diagnosed with PAS and were managed in the recruiting centers between 1 January 2010 and 31 December 2019 were included. Data were reanalyzed using machine learning (ML) models, and 2 models were created to predict outcomes using antepartum and perioperative features. ML model was conducted using python® programing language. The primary outcome was massive PAS-associated perioperative blood loss (intraoperative blood loss ≥2500 ml, triggering massive transfusion protocol, or complicated by disseminated intravascular coagulopathy). Other outcomes include prolonged hospitalization >7 days and admission to the intensive care unit (ICU). RESULTS: 727 women with PAS were included. The area under curve (AUC) for ML antepartum prediction model was 0.84, 0.81, and 0.82 for massive blood loss, prolonged hospitalization, and admission to ICU, respectively. Significant contributors to this model were parity, placental site, method of diagnosis, and antepartum hemoglobin. Combining baseline and perioperative variables, the ML model performed at 0.86, 0.90, and 0.86 for study outcomes, respectively. Ethnicity, pelvic invasion, and uterine incision were the most predictive factors in this model. DISCUSSION: ML models can be used to calculate the individualized risk of morbidity in women with PAS. Model-based risk assessment facilitates a priori delineation of management.

Placenta accreta risk-antepartum score in predicting clinical outcomes of placenta accreta spectrum: A multicenter validation study.

OBJECTIVE: To validate the use of placenta accreta risk-antepartum (PAR-A) score as a predictive tool of clinical outcomes of placenta accreta spectrum (PAS). METHODS: This is a prospective study, conducted in six PAS specialized centers in six different countries. The study was conducted between October 1, 2020 and March 31, 2021. Women who were provisionally diagnosed with PAS during pregnancy were considered eligible. A machine-learning-based PAR-A score was calculated. Diagnostic performance of the PAR-A score was evaluated using a receiver operating characteristic curve, for perioperative massive blood loss and admission to intensive care unit (ClinicalTrials.gov identifier NCT04525001). RESULTS: Of 97 eligible women, 86 were included. PAS-associated massive blood loss occurred in 10 patients (11.63%). Median PAR-A scores of massive blood loss in the current cohort were 8.9 (interquartile range 6.9-14.1). In predicting massive blood loss, the area under the curve of PAR-A scores was 0.85 (95% confidence interval [CI] 0.74-0.95), which was not significantly different from the original cohort (P = 0.2). PAR-A score prediction of intensive care unit admission was slightly higher compared with the original cohort (0.88, 95% CI 0.81-0.95; P = 0.06). CONCLUSION: PAR-A score is a novel scoring system of PAS outcomes, which showed external validity based on current data.

The relationship between oxidative stress markers and endometrial hyperplasia: A case-control study

Objective: Endometrial hyperplasia (EH) is considered an endometrial cancer precursor. This study aimed to determine the role of oxidative stress and thiol groups with antioxidant properties in EH pathogenesis. Materials and Methods: In our prospective case-control study, participants were washed with 5 mL of saline before the endometrial biopsy. Endometrial washing fluid was taken into microtubules, and thiol and disulfide levels were analyzed using the Ellman reagent. Results: A total of 108 patients were in the EH group and 84 patients in the control group. The total and native thiol levels were higher values in the control group (p<0.001, for both). Disulfide levels were higher in the EH group (p<0.001). Native/total thiol ratio and disulfide/total thiol ratio were higher in the EH group (p<0.001, for both). The analysis performed in the control group revealed a significant positive correlation between estradiol and disulfide levels (r=0.322, p=0.033). No significant correlation was found between estradiol and disulfide in the EH group. Conclusion: Oxidative stress level was higher in the washing fluids of patients with EH and this stress plays a role in the EH etiology.

Comparison of preoperative serum neopterin, periostin, indoleamine 2,3-dioxygenase, YKL-40, and tenascin-C levels with current tumor markers for early-stage endometrial cancer.

OBJECTIVE: To compare the predictive value of serum levels of neopterin, periostin, YKL-40, tenascin-C (TNC), and indoleamine 2,3-dioxygenase (IDO) with current tumor markers for the primary diagnosis of early-stage endometrial cancer. METHODS: A prospective cross-sectional study was conducted between January 2020 and November 2020. A total of 59 patients (38 women newly diagnosed with early-stage endometrial cancer [study group] and 21 women with benign endometrial pathologies [control group]) were enrolled. Blood samples were collected prior to surgery and underwent immunoassay analysis. RESULTS: Carcinoembryonic antigen (CEA), periostin, and IDO levels were significantly higher in the study group than the control group (P = 0.008, P = 0.034, and P = 0.003, respectively). Receiver operating characteristic curve analysis revealed that IDO, periostin, and CEA were good predictors of early-stage endometrial cancer (AUC = 0.733, 95% CI, 0.602-0.840, P < 0.002; AUC = 0.668, 95% CI, 0.533-0.785, P = 0.018; and AUC = 0.709, 95% CI, 0.576-0.820, P = 0.002, respectively). Correlation analysis revealed no significant correlation of any biomarker with age or body mass index in either the control or study group. CONCLUSION: Serum CEA, periostin, and IDO levels were significantly higher in women with endometrial cancer than in those without cancer. These results may help identify new markers for diagnosing endometrial cancer.

COMPARISON OF TVUS, MRI, AND FROZEN SECTION METHODS IN PREOPERATIVE DETECTION OF MYOMETRIAL INVASION IN PATIENTS WITH ENDOMETRIAL CANCER.

We aimed to evaluate the depth of myometrial invasion preoperatively with transvaginal ultrasound, magnetic resonance imaging, and frozen section examination techniques in patients diagnosed with endometrial cancer. Our study included 65 patients. Transvaginal ultrasound and magnetic resonance imaging were performed in study patients in the preoperative period. Frozen section examination was performed in all hysterectomy samples obtained from all study patients. Data were analyzed with SPSS Statistics 22.0 program. The sensitivity of transvaginal ultrasound in determining the depth of myometrial invasion was 88.64%, specificity 90.48%, positive predictive value 95.12%, and negative predictive value 79.17%. For magnetic resonance imaging, the sensitivity was 63.64%, specificity 95.24%, positive predictive value 96.55%, and negative predictive value 55.56%. In addition to the frozen section examination, which is the gold standard in determining the myometrial invasion depth, transvaginal ultrasound and magnetic resonance imaging have become commonly used methods for this purpose in recent years. Ultrasound examination performed by an experienced specialist is superior to magnetic resonance imaging as it is fast, inexpensive, and associated with higher sensitivity.

The ability of various cerebroplacental ratio thresholds to predict adverse neonatal outcomes in term fetuses exhibiting late-onset fetal growth restriction.

OBJECTIVES: Our primary aim was to evaluate the ability of various cerebroplacental ratio (CPR) reference values suggested by the Fetal Medicine Foundation to predict adverse neonatal outcomes in term fetuses exhibiting late-onset fetal growth restriction (LOFGR). Our secondary aim was to evaluate the effectiveness of other obstetric Doppler parameters used to assess fetal well-being in terms of predicting adverse neonatal outcomes. METHODS: This was a retrospective cohort study of 317 pregnant women diagnosed with LOFGR at 37-40 weeks of gestation between January 1, 2016, and September 1, 2019. Receiver operating characteristic (ROC) curves were drawn to determine the predictive performance of CPR <1, CPR <5th or <10th percentile, and umbilical artery pulsatility (PI) >95th percentile in terms of predicting adverse neonatal outcomes. RESULTS: Pregnant women exhibiting LOFGR who gave birth in our clinic during the study period at a mean of 38 gestational weeks (minimum 37+0; maximum 40+6 weeks); the median CPR was 1.51 [interquartile range (IQR) 1.12-1.95] and median birthweight 2,350 g (IQR 2,125-2,575 g). The CPR <5th percentile best predicted adverse neonatal outcomes [area under the curve (AUC) 0.762, 95% confidence interval (CI) 0.672-0.853, p<0.0001] and CPR <1 was the worst predictor (AUC 0.630, 95% CI 0.515-0.745, p=0.021). Of other Doppler parameters, neither the umbilical artery systole/diastole ratio nor the mid-cerebral artery to peak systolic velocity ratio (MCA-PSV) predicted adverse neonatal outcomes (AUC 0.598, 95% CI 0.480-0.598, p=0.104; AUC 0.521, 95% CI 0.396-0.521, p=0.744 respectively). CONCLUSIONS: The CPR values below the 5th percentile better predicted adverse neonatal outcomes in pregnancies complicated by LOFGR than the UA PI and CPR <1 by using Fetal Medicine Foundation reference ranges.

Risk factors for cervical stromal involvement in endometrioid-type endometrial cancer.

OBJECTIVE: The aim of this study was to identify predictors of cervical stromal involvement in women with endometrioid-type endometrial cancer (EEC). METHODS: A total of 795 patients with EEC who underwent comprehensive surgical staging including pelvic and para-aortic lymph node dissection between January 2007 and December 2018 were retrospectively analyzed. Data including age, menopausal status, serum CA-125 levels, tumor size, lymphovascular space invasion (LVSI), depth of myometrial invasion, positive peritoneal cytology, cervical stromal involvement, histologic grade, recurrence, and follow-up duration were recorded. RESULTS: Median follow up was 49 months. Cervical stromal invasion was found in 88 patients. Multivariate analysis revealed that presence of LVSI (hazard ratio [HR] 2, 95% confidence interval [CI] 1.02-4.25, P = 0.045), a primary tumor diameter of at least 3 cm (HR 3, 95% CI 1.31-7.25, P = 0.010), and at least 50% deep myometrial invasion (HR 2.7, 95% CI 1.37-5.41, P = 0.004) were independent risk factors for cervical stromal involvement in patients with EEC. CONCLUSION: Our study results suggest that presence of LVSI, a primary tumor diameter of at least 3 cm, and LVSI of at least 50% seem to be independent predictors of cervical involvement in women with EEC.

Prediction of success of uterus-preserving management in women with placenta accreta spectrum (CON-PAS score): A multicenter international study.

OBJECTIVE: To create a model for prediction of success of uterine-preserving procedures in women with placenta accreta spectrum (PAS). METHODS: PAS-ID is a multicenter study that included 11 centers from 9 countries. Women with PAS, who were managed between January 1, 2010 and December 31, 2019, were retrospectively included. Data were split into model development and validation cohorts, and a prediction model was created using logistic regression. Main outcome was success of uterine preservation. RESULTS: Out of 797 women with PAS, 587 were eligible. Uterus-preserving procedures were successful in 469 patients (79.9%). Number of previous cesarean sections (CS) was inversely associated with management success (adjusted odds ratio [aOR] 0.02, 95% confidence interval [CI] 0.001-3.63 with five previous CS). Other variables were complete placental invasion (aOR 0.14, 95% CI 0.05-0.43), type of CS incision (aOR 0.04, 95% CI 0.01-0.25 for classical incision), compression sutures (aOR 2.48, 95% CI 1.00-6.16), accreta type (aOR 3.76, 95% CI 1.13-12.53), incising away from placenta (aOR 5.09, 95% CI 1.52-16.97), and uterine resection (aOR 102.57, 95% CI 3.97-2652.74). CONCLUSION: The present study provides a prediction model for success of uterine preservation, which may assist preoperative and intraoperative decisions, and promote incorporation of uterine preservation procedures in comprehensive PAS protocols.

The investigation of serum levels of ADAMTS 5 and 8 (the A disintegrin and metalloproteinase with thrombospondin motifs) in the etiology of endometrial cancer.

The aim of this study was to investigate the serum levels of the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5 and 8 in patients diagnosed with endometrial cancer. Our study included 41 patients diagnosed with endometrial cancer. The control group consisted of 41 patients diagnosed with benign endometrial pathology. The serum samples were centrifuged and stored at -80 °C. The serum levels of ADAMTS were significantly higher (p<.001), whereas the levels of ADAMTS 8 were significantly lower in patients diagnosed with cancer (p<.001). In addition to the presence of known factors in the aetiology of endometrial cancer, the effect of inflammatory factors and some new proteins has centred on the causes of tumourigenesis in recent years. In this sense, these proteins, called the ADAMTS, are the source of new studies.Impact StatementWhat is already known on this subject? When the recent studies about endometrial cancer are evaluated, it is seen that the effects of chronic inflammation and cytokines have gained importance in its aetiology. The A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) gene family consist of 19 proteases that play essential role in the formation of the extracellular matrix (ECM) and interact with inflammatory cytokines. These proteases and their substrates provide a wide range of functions in different tissues, including ECM remodelling, angiogenesis, fibrosis and coagulation.What the results of this study add? ADAMTS 5, which causes the degradation of the ECM with Aggrecanase activity, was found to be significantly higher in patients diagnosed with cancer and ADAMTS 8 with anti-angiogenesis activity was significantly lower in patients diagnosed with endometrial cancer.What the implications are of these findings for clinical practice and/or further research? In this study, it is understood that the effect of inflammatory mediators is remarkably important in the aetiology of endometrial cancer, as in many types of organ specific cancer.

RETROSPECTIVE ANALYSIS OF BORDERLINE OVARIAN TUMORS: OUTCOMES AT A SINGLE CENTER.

We wanted to discuss our experiences in the approach to borderline ovarian tumors, which constitute a group different from epithelial ovarian tumors with respect to their biological structure in line with retrospective information gathered from our cases. A total of 25 patients operated on for the indication of adnexal masses diagnosed as borderline ovarian tumors based on frozen section results were included in our study. Patient age, tumor diameter, tumor markers and surgeries performed were discussed in the light of the literature. Statistical analyses were performed using the SPSS software. The patient mean age was 43.84±11.34 years. The mass was localized in the right (n=13), left (n=11) or both (n=1) adnexal regions. The mean tumor diameter was 12.9±5.84 cm. Histopathologic examination established the diagnosis of serous borderline (n=14 patients) and mucinous borderline (n=11) ovarian tumors. Although the results of our study are consistent with current literature data, a greater number of current studies should be performed on borderline ovarian tumors, which are defined as a class of tumors different from epithelial ovarian tumors.

The Effect of Prognostic Factors and Adjuvant Radiotherapy on Survival in Patients with High-Grade Early-Stage Endometrial Cancer: A Retrospective Clinical Study.

BACKGROUND This retrospective clinical study aimed to investigate the effect of prognostic factors and adjuvant radiotherapy in patients with high-grade early-stage endometrial cancer on overall survival (OS) and disease-free survival (DFS). MATERIAL AND METHODS The medical records of patients diagnosed with high-grade, early stage (I or II) endometrial adenocarcinoma who had received adjuvant radiotherapy after surgery were reviewed. RESULTS Seventy-nine patients included 39 patients (49.4%) with stage II endometrial cancer, 25 patients (31.6%) with histologic grade 3 tumors, and 47 patients (59.5%) with endometrial cancer showing lymphovascular space invasion (LVSI). There were 45 patients (57.0%) who received external pelvic radiotherapy with an average dose of 46.0 Gy (range, 11.2-50.4 Gy), and 34 patients (43.0%) received vaginal brachytherapy (VBT) with an average dose of 21.5 Gy (range, 10-36 Gy). Multivariate analysis showed that tumor stage (HR, 4.066; 95% CI, 1.227-13.467; p=0.022) and histologic grade (HR, 16.652; 95% CI, 4.430-62.589; p<0.001) were independent predictors for OS. Increased serum CA-125 levels (HR, 1.136; 95% CI, 0.995-1.653; p=0.047) and histologic grade (HR, 3.236; 95% CI, 1.107-15.156; p=0.015) were independent predictors for DFS. Adjuvant radiotherapy was not found to be significantly associated with improved OS (HR, 1.259; 95% CI, 0.518-3.058; p=0.612) or DFS (HR, 1.056; 95% CI, 0.994-1.123; p=0.078). CONCLUSIONS This retrospective study showed that in high-grade early-stage endometrial cancer treated with postoperative adjuvant radiotherapy, independent predictors for OS were tumor stage and grade. Adjuvant radiotherapy was not associated with improved OS or DFS.

Associations between second-trimester amniotic fluid levels of ADAMTS4, ADAMTS5, IL-6, and TNF-α and spontaneous preterm delivery in singleton pregnancies.

Background We investigated the roles of inflammatory cytokines and the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family in the etiopathogenesis of spontaneous preterm delivery by comparing the ADAMTS4, ADAMTS5, interleukin (IL)-6, and tumor necrosis factor-α (TNF-α) levels in second-trimester amniotic fluid between pregnant women with preterm birth and term controls. Methods All pregnant women who underwent second-trimester amniocentesis for genetic analysis between January 1, 2016, and January 1, 2018, were enrolled in this study. From this cohort, 22 patients who subsequently experienced spontaneous preterm delivery before 34 weeks of pregnancy formed the study group, and 22 age- and body mass index (BMI)-matched patients without preterm birth constituted the control group. Results No significant differences were observed between the preterm birth and control groups in terms of age, BMI, obstetric history of preterm delivery, gestational age at amniocentesis, or indication for amniocentesis. The mean amniotic fluid levels of ADAMTS4 and ADAMTS5 were significantly increased in the preterm birth group compared to the control group (248.3±22.6 and 182.4±19.8 pg/mL, P=0.012; and 198.6±21.6 and 159.1±21.7 pg/mL, P=0.035, respectively). Significantly increased IL-6 and TNF-α levels were also detected in the amniotic fluid of women who experienced spontaneous preterm delivery, relative to controls (142.1±16.2 and 95.8±16.4 pg/mL, P<0.001; and 139.4±12.5 and 89.6±11.2 pg/mL, P<0.001, respectively). Conclusion The results of this study imply that increased mid-trimester amniotic fluid levels of ADAMTS4, ADAMTS5, IL-6, and TNF-α play an important role in the pathophysiology of spontaneous preterm delivery.